Gray et al. in J. Am. Chem. Soc., 84, 89 (1962) and U.S. Pat. No. 3,127,413 disclose octahydroisoindoles of the formula: ##STR1## The octahydroisoindoles are useful as tranquilizing agents and for potentiating the action of barbiturates.
Processes for preparing trisubstituted perhydro isoindolines of the following formula are described by Achini et al, Helvetica Chimica Acta, 57, 572 (1974): ##STR2##
Otzenberger et al., J. Org. Chem., 39, 319 (1974) disclose a compound of formula: ##STR3## No utility is disclosed.
Rehse et al., Arch. Pharm. (Weinheim), 312, 982 (1979), disclose a compound of formula: ##STR4## The authors disclose this compound is a dopamine agonist.
German Patent DE 3614906 discloses a compound of formula: ##STR5## The patentee discloses this compound is a plant fungicide.
Dunet et al., Bull. Soc. Chim. France, 1956, 906, disclose a compound of formula: ##STR6## The authors do not disclose a utility for this compound.
Pogossyan et al., Arm. Khim. Zh., 33, 157 (1980), disclose compounds having the formula: ##STR7## The authors disclose these compounds are reserpine antagonists.
Rashidyan et al., Arm. Khim. Zh., 23,474 (1970), disclose compounds of formula: ##STR8## The authors do not disclose a utility for these compounds.
Pogossyan et al., Arm. Khim. Zh., 32, 151 (1979), disclose a compound of formula: ##STR9## The authors do not disclose a utility for this compound.
Rashidyan et al., Arm. Khim. Zh., 21, 793 (1968), disclose a compound having the formula: ##STR10## The authors do not disclose a utility for this compound.
Grieco et al., J. Chem. Soc., Chem. Soc., 1987, 185, disclose a compound of formula: ##STR11## The authors do not disclose a utility for this compound.
Larsen et al., J. Chem. Soc., 108, 3512 (1986), disclose a compound having the formula: ##STR12## The authors do not disclose a utility for this compound.
German Patent 3721723 (Hoechst AG) describes substituted 6-oxo-decahydroisoquinolines of the formula: ##STR13## These compounds are useful as sedatives.
Archer et al., J. Med. Chem., 30, 1204 (1987), disclose a compound having the formula: ##STR14## The authors do not disclose a utility for this compound.
Deslongchamps et al., Can. J. Chem., 53, 3613 (1975), disclose a compound having the formula: ##STR15## The authors do not disclose a utility for this compound.
Jirkovsky et al., Coll. Czech. Chem. Commun., 29, 400 (1964), disclose a compound having the formula: ##STR16## The authors do not disclose a utility for this compound.
Meyers et al., J. Org. Chem., 51, 872 (1986), disclose a compound of formula: ##STR17## The authors do not disclose a utility for this compound.
Bartmann et al., Synth. Commun., 18, 711 (1988), disclose compounds of formula: ##STR18## The authors do not disclose a utility for these compounds.
Compounds of the present invention demonstrate sigma receptor affinity. It is this sigma receptor affinity of the compounds of the present invention which makes them so advantageous over the compounds in the prior art. Traditionally, antipsychotic agents have been potent dopamine receptor antagonists. For example, phenothiazines such as chlorpromazine and most butyrophenones such as haloperidol are potent dopamine receptor antagonists. These dopamine receptor antagonists are associated with a high incidence of side effects, particularly Parkinson-like motor effects or extra-pyramidal side-effects (EPS), and dyskinesias including tardive dyskinesias at high doses. Many of these side effects are not reversible even after the dopamine receptor antagonist agent is discontinued.
The present invention is related to antipsychotic agents which are sigma receptor antagonists, not traditional dopamine receptor blockers known in the art, and therefore the compounds of the present invention have low potential for the typical movement disorder side-effects associated with the traditional dopamine antagonist antipsychotic agents while they maintain the ability to antagonize aggressive behavior and antagonize hallucinogenic-induced behavior.